JAG1 promotes migration, invasion, and adhesion of triple-negative breast cancer cells by promoting angiogenesis / 南方医科大学学报

OBJECTIVE@#To investigate the effect of JAG1 on the malignant phenotype of triple-negative breast cancer (TNBC) and its role in angiogenesis in breast cancer microenvironment.@*METHODS@#The expressions of Notch molecules were detected in human TNBC 231 and 231B cells using RT-qPCR. Five female nude mice were inoculated with 231 cells and another 5 with 231B cells into the mammary fat pads, and 4-6 weeks later, the tumors were collected for immunohistochemical and immunofluorescence tests. 231 cells and 231B cells were treated with recombinant JAG (rJAG) protein and DAPT, respectively, and changes in their malignant phenotypes were assessed using CCK-8 assay, Hoechst 33258 staining, wound healing assay, Transwell chamber assay and endothelial cell adhesion assay. Western blotting was used to detect the changes in the expressions of proteins related with the malignant phenotypes of 231 and 231B cells. The effects of conditioned medium (CM) derived from untreated 231 and 231 B cells, rJAG1-treated 231 cells and DAPT-treated 231B cells on proliferation and tube formation ability of cultured human umbilical vein endothelial cells (HUVECs) were evaluated using CCK-8 assay and tube-forming assay.@*RESULTS@#The expression of JAG1 was higher in 231B cells than in 231 cells (P < 0.05). Tumor 231B showed higher expression of VEGFA and CD31. Compared with 231-Blank group, the migration, invasion and adhesion of 231 cells in 231-rJAG1 were significantly enhanced (P < 0.05). Protein levels of Twist1 and Snail increased (P < 0.01), anti-apoptotic protein Bcl-2 increased (P < 0.05), while DAPT inhibited the related phenomena and indicators of 231B. The 231-rJAG1-CM increased the cell number and tubule number of HUVEC (P < 0.05).@*CONCLUSION@#JAG1 may affect the malignant phenotype of TNBC and promote angiogenesis in the tumor microenvironment.

Agkistrodon halys venom antitumor component-I inhibits vasculogenic mimicry in triple-negative breast cancer cells in vitro by down-regulating MMP2 / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effect of agkistrodon halys venom antitumor component-I (AHVAC-I) on vasculogenic mimicry (VM) formation in triple-negative breast cancer MDA-MB-231 cells and explore its possible mechanism.@*METHODS@#CCK8 assay was used to determine the optimal concentration of AHVAC-I for cell treatment based on its halfinhibitory concentration (IC50). MDA-MB-231 cells were treated with different concentrations of AHVAC-I or 5-Fu, and the changes in vasomimetic capacity of the cells were examined using Matrigel assay. The expression levels of matrix metalloproteinase-2 (MMP2) and MMP9 in the treated cells were detected using quantitative PCR and Western blotting.@*RESULTS@#Compared with the control treatment with culture medium, treatment with 5, 10 and 20 μg/mL AHVAC-I significantly reduced vasomimetic ability of MDA-MB-231 cells in a dose-dependent manner (P < 0.01). MMP2 supplementation obviously restored the vasomimetic ability of the cells inhibited by AHVAC-I.@*CONCLUSION@#AHVAC-I inhibits VM formation in triplenegative breast cancer cells in vitro by down-regulating MMP2 production.

(+)-corynoline Regulates the Proliferation,Stemness and Apoptosis of Triple Negative Breast Cancer Cells / 中国医学科学院学报

Objective To explore the performance and mechanism of(+)-corynoline in treating triple negative breast cancer MDA-MB-436 cells and thus provide an option for the development of drugs against this cancer. Methods The viability,proliferation,apoptosis and migration/invasion of MDA-MB-436 cells treated with(+)-corynoline were detected by CCK-8 assay,colony formation assay,flow cytometry and Transwell assay,respectively.Furthermore,Western blotting was employed to determine the expression of related proteins,and RNA-Seq was performed for the MDA-MB-436 cells treated with(+)-corynoline. Results (+)-corynoline inhibited the proliferation and stemness and promoted the apoptosis of MDA-MB-436 cells.Further,(+)-corynoline may activate the oxidative phosphorylation pathway to play a role in inhibiting triple negative breast cancer. Conclusion (+)-corynoline can inhibit triple negative breast cancer cells,which helps to address the poor efficacy of existing chemotherapeutics and facilitate the development of drugs against this cancer.

The Apocrine Profile of Triple-negative Breast Carcinomas in Patients Aged 45 Years or Younger: favorable but rare features / Perfil apócrino em carcinomas mamários triplonegativos de pacientes até 45 anos: característica favorável, ainda que rara

Abstract Objective Triple-negative breast carcinomas (TNBCs) represent a heterogeneous group of neoplasias, even though they generally exhibit a clinically more aggressive phenotype, and are more prevalent in young women. To date, targeted therapies for this group of tumors have not been defined. The aim of this study was to evaluate the frequency of the apocrine subtype in TBNCs from premenopausal patients as defined by the immunohistochemical expression of the androgen receptor (AR) and its association with: histological type; tumor grade; proliferative activity; epidermal growth factor receptor (EGFR) expression; and a basal-like phenotype. Methods A total of 118 tumor samples from patients aged 45 years or younger were selected and reviewed according to histological type and grade. Ki-67 expression was also evaluated. Immunohistochemical expression of the AR, basal cytokeratin ⅚, and EGFR expression were analyzed in tissue microarrays. The apocrine subset was defined by AR-positive expression. The basal-like phenotype was characterized by cytokeratin ⅚ and/or EGFR expression. Results An apocrine profile was identified in 6/118 (5.1%) cases. This subset of cases also exhibited a lower rate of Ki-67 expression (17.5% versus 70.0%, p= 0.02), and a trend toward a lower histological grade (66.7% versus 27.9%, p= 0.06). Conclusions The apocrine subtype of TNBCs is rare among premenopausal women, and it tends to present as carcinomas of lower grade and lower proliferative activity, suggesting a less aggressive biological phenotype.

Resumo Objetivo Carcinomas mamários triplo-negativos representam um grupo heterogêneo de neoplasias, embora geralmente exibam fenótipo clinicamente mais agressivo e sejam mais prevalentes em mulheres jovens. Até o presente, terapias-alvo para esses grupos não foram definidas. O objetivo deste estudo foi avaliar a frequência do subtipo apócrino em carcinomas mamários triplo-negativos de mulheres na pré-menopausa, definido pela expressão imuno-histoquímica do receptor de androgênio, e sua associação com tipo histológico, grau histológico, atividade proliferativa, expressão do receptor do fator de crescimento epidérmico (EGFR) e o fenótipo basal-símile. Métodos Foram selecionadas 118 amostras de tecido tumoral de pacientes com até 45 anos de idade. As amostras foram revisadas quanto a tipo e grau histológicos e expressão do Ki-67. A expressão imuno-histoquímica de receptor de androgênio, citoqueratina basal ⅚, e do EGFR foram analisadas em amostras de microarranjos de tecido. O subtipo apócrino foi definido pela positividade do receptor de androgênio. O fenótipo basal-símile foi caracterizado pela expressão da citoqueratina ⅚ e/ou do EGFR. Resultados O perfil apócrino foi identificado em 6/118 (5,1%) casos. Este subgrupo apresentou menor fração de expressão do Ki-67 (17,5% versus 70,0%, p= 0,02) e uma tendência a menor grau histológico (66,7% versus 27,9%, p= 0,06). Conclusões O subtipo apócrino dos carcinomas mamários triplo-negativos é raro em mulheres na pré-menopausa, e tende a se apresentar como carcinomas de menor grau e menor atividade proliferativa, sugerindo fenótipo biológico menos agressivo.

Triple-negative breast cancer survival in Iranian patients

This study focused on triple-negative breast cancer [TNBC] that is characterized by the lack of expression of estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER-2]. The primary goal of this study was to describe the relation between triple-negative receptor status and survival. This is the first study about triple-negative breast cancer in our community of the 1541 patients diagnosed with breast cancer between 2002 and 2007 at the Cancer Institute [Tehran, Iran]. 107 patients were identified as TNBC and 107 patients were randomly selected as non-TNB. HER-2, ER and PR status were assessed by immunohistochemistry [IHC]. Analyses of their collected data were performed retrospectively and then clinical and pathologic parameters were compared between two groups. In multivariate analysis, a significantly decreased overall survival was observed for patients with TNBC compared with non-TNBC [55.7 months versus 60.7 mounts; 95%CI: 51.1-60.3 and 57.9-63.5 for TNBC and non-TNBC respectively, P=0.0008]. The 2- and 5-year estimates for overall survival were 69.8% and 62.3% for TNBC, and 90% and 83% for non-TNBC, respectively. During the study period, 36 [33.6%] patient of TNBC and 14 [13.1%] of non-TNBC presented local recurrence. Significantly decreased disease-free survival was also observed for patients with TNBC compared with non-TNBC [P=0.0004]. The 2- and 5-year estimates for disease-free survival were 68% and 63% for TNBC; and 89% and 82% for non-TNBC, respectively. Significantly decreased distant metastasis free survival was also observed for patients with TNBC compared with non-TNBC [54.4 mounts versus 61.7 mounts; 95%CI: 49.8-59.0 and 59.1-64.4 for TNBC and non-TNBC respectively, P=0.0004]. Triple negative breast cancer has a biologic aggressive behavior and poor prognosis. Therefore aggressive treatment and regular follow-up in early stage of diagnosis can be a significant impact on their prognosis.